G6pd Deficiency And Hyperbilirubinemia In Newborn Baby(Prospective Study )
Main Article Content
Keywords
G6PD deficiency, hyperbilirubinemia, newborn, gene
Abstract
Background: The most prevalent enzyme deficit in humans is glucose-6-phosphate dehydrogenase insufficiency. Objectives**To investigate the significance of G6PD deficiency in hyperbilirubinemic newborns.
Aims: To assess additional parameters associated with newborn hyperbilirubinemia.
From December 2017 to April 2018, two hundred newborn babies were enrolled in a prospective study at the Neonatal Care Unit of Child's Hospital ; one hundred were diagnosed with clinical and biochemical neonatal jaundice, while the other hundred served as a control group. The activity of G6PD was measured by a met haemoglobin reduction test, with both groups further classified into G6PD deficient and normal subsets.Results G6PD deficiency was found in 25% of infants with jaundice but only 8% of those without jaundice (the control group). Twenty of the G6PD-deficient individuals were men (80%) and five were women (20%).Recommendations and findingsThere is an elevated risk of newborn hyperbilirubinemia associated with G6PD deficiency, and a considerable percentage of affected infants (10-40%) would need an exchange blood transfusion as a result.
In high-risk communities like ours, screening for G6PD in cord blood is one option to consider. Early diagnosis of the enzyme deficit by newborn screening is recommended in a community with a high prevalence rate so that necessary treatments may be taken to prevent the consequences of hemolysis and future issues of neonatal jaundice owing to G6PD deficiency.
Goals of Research
1. To investigate the significance of G6PD deficiency in hyperbilirubinemic newborns.
2. to investigate additional potential causes of newborn hyperbilirubinemia.
References
1. Jennifere.Frank, American Academy MALMC. Of Family Diagnosis Physicians, and 2005: Management 72:1277-82of G6PD deficiency
2. Lazzatto L . Metha A. G6PD deficiency .In Metabolic and Molecular bases of Inherited disease. Editors: Scriver, Charles R. , Arthur I Beaude, and Williams S. , 7th ed, New York, MeGraw Hill, 1995:3367-98
3. Segel G B. Enzymatic defects In: Behrman R.B ., Kliegman R.M ., JensonHB, Stanton BF.(Editors), Nelson Textbook of Pediatrics, 18? ed. Philadelphia, WB Saunders, 2007; 468: 2039-42. .
4. LuzzattoL. Glucose-6-phosphate dehydrogenase deficiency and hemolytle anemia. In: Nathan D.G ., Orkin S.H ., Ginsburg D. , Look A. T ., (Editors)Nathan and Oski's Hematology of Infancy and Childhood, Sixth ed ., New York, Saunders, 2003; 17:721-38
5. Beutler E. The molecular biology of G6PD variants and other red cell enzyme defects. Ann Rev Med 1992; 43: 47-59.
6. Hassan M K, Taha J Y, Al-Naama L M, Widad N M, and Jasim S N.6.Frequency of hemoglobinopathies and glucose -6- phosphate dehydrogenase deficiency in Basra. Eastern Mediterranean health journal, 2003; 9:49-53.
7. Margaret JA, Adams MJ, Naylor CE. Glucose-6-phsphate dehydrogenase mutationcausingenzymedeficiency,Blood 1996; 87; 2974-2982 .
8. Mehta deficiency. A,Mason Baillieres PJ,Best Vulliamy Pract Res TJ. Clin Glucose-6-phosphate Haematol 2000; 13: 21-38.dehydrogenase.
9. Chen E Y, "Sequence of human glucose-6-phosphate dehydrogenase cloned in plasmids and a yeast artificial chromosome"Genomics1991; 10:792
10. Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Hyperbilirubinemia: Insights on Pathophysiology, Diagnosis, and Gene Variants in Disease Heterogeneity Heng Yang Lee1, Azlin Ithnin2, Raja Zahratul Azma2, Ainoon Othman3, Armindo Salvador4,5,6 and Fook Choe Cheah1*
11. Greco C, Arnolda G, Boo NY, Iskander IF, Okolo AA, Rohsiswatmo R, et al. Neonatal jaundice in low- and middle-income countries: lessons and future directions from the 2015 Don Ostrow Trieste Yellow Retreat. Neonatology. (2016) 110:172–80. doi: 10.1159/000445708
12. Lie-Injo LE, Virik HK, Lim PW, Lie AK, Ganesan J. Red cell metabolism and severe neonatal jaundice in WestMalaysia. Acta Haematol. (1977) 58:152–60. doi: 10.1159/000207822
13. Singh H. Glucose-6-phosphate dehydrogenase deficiency: a preventable cause of mental
retardation. Br Med J (Clin Res Ed). (1986) 292:397–8. doi: 10.1136/bmj.292.6517.397
14. Wong FL, Ithnin A, Othman A, Cheah FC. Glucose-6-phosphate dehydrogenase (G6PD)-deficient infants: enzyme activity and gene variants as risk factors for phototherapy in the first week of life. J Paediatr Child
15. Health. (2017) 53:705–10. doi: 10.1111/jpc.13509
16. Kaplan M, Wong RJ, Stevenson DK. Hemolysis and glucose-6-phosphate dehydrogenase deficiency-related neonatal hyperbilirubinemia. Neonatology. (2018) 114:223–5. doi: 10.1159/000489820
17. Pandolfi PP, Sonati F, Rivi R, Mason P, Grosveld F, Luzzatto L. Targeted disruption of the housekeeping gene encoding glucose 6-phosphate dehydrogenase (G6PD): G6PD is dispensable for pentose synthesis but essential for defense against oxidative stress. EMBO J. (1995) 14:5209–15. doi: 10.1002/j.1460 2075.1995.tb00205.x
18. Low FM, Hampton MB, Winterbourn CC. Peroxiredoxin 2 and peroxide metabolism in the erythrocyte. Antioxid Redox Signal. (2008) 10:1621–30. doi: 10.1089/ars.2008.2081
19. Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. (2009) 30:1–12. doi: 10. 1016/j.mam.2008.08.006
20. Luzzatto L, Arese P. Favism and glucose-6-phosphate dehydrogenase deficiency. N Engl J Med. (2018) 378:60–71. doi: 10.1056/nejmra1708111
21. Cheah FC, Peskin AV, Wong FL, Ithnin A, Othman A, Winterbourn CC. Increased basal oxidation of peroxiredoxin 2 and limited peroxiredoxin recycling in glucose-6-phosphate dehydrogenase-deficient erythrocytes from newborn infants. FASEB J. (2014) 28:3205–10. doi: 10.1096/fj.14-250050
22. Beutler E. The genetics of glucose-6-phosphate dehydrogenase deficiency. Semin Hematol. (1990) 27:137–64.
23. Coelho PMBM, Salvador A, Savageau MA. Relating mutant genotype to phenotype via quantitative behavior of the NADPH redox cycle in human erythrocytes. PLoS One. (2010) 5:e13031. doi: 10.1371/journal.pone.0013031
24. Corrons JL, Alvarez R, Pujades A, Zarza R, Oliva E, Lasheras G, et al. Hereditary non-spherocytic haemolytic anaemia due to red blood cell glutathione synthetase deficiency in four unrelated patients from Spain: clinical and molecular studies. Br J Haematol. (2001) 112:475–82. doi: 10. 1046/j.1365-2141.2001.02526.x
25. Minucci A, Moradkhani K, Hwang MJ, Zuppi C, Giardina B, Capoluongo E. Glucose-6-phosphate dehydrogenase (G6PD) mutations database:review of the “old” and update of the new mutations. Blood Cells Mol Dis. (2012) 48:154–65. doi: 10.1016/j.bcmd.2012.01.001
26. Gómez-Manzo S, Marcial-Quino J, Vanoye-Carlo A, Serrano-Posada H, Ortega-Cuellar D, González-Valdez A, et al. Glucose-6-phosphate dehydrogenase: update and analysis of new mutations around the world. Int J Mol Sci. (2016) 17:2069. doi: 10.3390/ijms17122069
27. Bahr TM, Lozano-Chinga M, Agarwal AM, Meznarich JA, Yost CC, Li P, et al. A novel variant in G6PD (c.1375C>G) identified from a Hispanic neonate with extreme hyperbilirubinemia and low G6PD enzymatic activity. Neonatology. (2020) 117:532–5. doi: 10.1159/000510300
28. Tong Y, Liu B, Zheng H, Bao A, Wu Z, Gu J, et al. A novel G6PD deleterious variant identified in three families with severe glucose-6- phosphate dehydrogenase deficiency. BMC Med Genet. (2020) 21:150. doi:10.1186/s12881-020-01090-2
29. Alina MF, Azma RZ, Norunaluwar J, Azlin I, Darnina AJ, Cheah FC, et al. Genotyping of Malaysian G6PD-deficient neonates by reverse dot blot flowthrough hybridisation. J Hum Genet. 65(3), 263-270. Erratum in J Hum Genet. (2020) 65:635. doi: 10.1038/s10038-019-0700-7
30. Malik S, Zaied R, Syed N, Jithesh P, Al-Shafai M. Seven novel glucose- 6-phosphate dehydrogenase (G6PD) deficiency variants identified in the Qatari population. Hum Genomics. (2021) 15:61. doi: 10.1186/s40246-021-0 0358-9
31. Xu W, Westwood B, Bartsocas CS, Malcorra-Azpiazu JJ, Indrák K, Beutler E. Glucose-6 phosphate dehydrogenase mutations and haplotypes in various ethnic groups. Blood (1995) 85:257–63. doi: 10.1182/blood.V85. 1.257.bloodjournal851257
32. Chen TL, Yang HC, Hung CY, Ou MH, Pan YY, Cheng ML, et al. Impaired embryonic development in glucose-6-phosphate dehydrogenasedeficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism. Cell Death Dis. (2017) 8:e2545. doi: 10. 1038/cddis.2016.463
33. Yoshida A, Beutler E, Motulsky AG. Human glucose-6-phosphate dehydrogenase variants. Bull World Health Organ. (1971) 45:243–53.
34. He Y, Zhang Y, Chen X, Wang Q, Ling L, Xu Y. Glucose-6-phosphate dehydrogenase deficiency in the Han Chinese population: molecular characterization and genotype-phenotype association throughout an activity distribution. Sci Rep. (2017) 10:17106. doi: 10.1038/s41598-020-74200-y
35. Boonyuen U, Chamchoy K, Swangsri T, Saralamba N, Day NP, Imwong M. Detailed functional analysis of two clinical glucose-6- phosphate dehydrogenase (G6PD) variants, G6PDViangchan and G6PDViangchan+Mahidol: decreased stability and catalytic efficiency contribute to the clinical phenotype. Mol Genet Metab. (2016) 118:84–91. doi: 10.1016/j.ymgme.2016.03.008
36. Pietrapertosa A, Palma A, Campanale D, Delios G, Vitucci A, Tannoia N. Genotype and phenotype correlation in glucose-6-phosphate dehydrogenase deficiency. Haematologica. (2001) 86:30–5.
37. Scopes DA, Bautista JM, Naylor CE, Adams MJ, Mason PJ. Amino acid substitutions at the dimer interface of human glucose-6-phosphate dehydrogenase that increase thermostability and reduce the stabilising effect of NADP. Eur J Biochem. (1998) 251:382–8. doi: 10.1046/j.1432-1327.1998. 2510382.x
38. Mason PJ, Bautista JM, Gilsanz F. G6PD deficiency: the genotype-phenotype association. Blood Rev. (2007) 21:267–83. doi: 10.1016/j.blre.2007.05.002
39. Gómez-Manzo S, Terrón-Hernández J, De la Mora-De la Mora I, González-Valdez A, Marcial-Quino J, García-Torres I, et al. The stability of G6PD is affected by mutations with different clinical phenotypes. Int J Mol Sci. (2014) 15:21179–201. doi: 10.3390/ijms151121179
40. Ainoon O, Alawiyah A, Yu YH, Cheong SK, Hamidah NH, Boo NY, et al. Semiquantitative screening test for G6PD deficiency detects severe deficiency but misses a substantial proportion of partiallydeficient females. Southeast Asian J Trop Med Public Health. (2003)34:405–14.
2. Lazzatto L . Metha A. G6PD deficiency .In Metabolic and Molecular bases of Inherited disease. Editors: Scriver, Charles R. , Arthur I Beaude, and Williams S. , 7th ed, New York, MeGraw Hill, 1995:3367-98
3. Segel G B. Enzymatic defects In: Behrman R.B ., Kliegman R.M ., JensonHB, Stanton BF.(Editors), Nelson Textbook of Pediatrics, 18? ed. Philadelphia, WB Saunders, 2007; 468: 2039-42. .
4. LuzzattoL. Glucose-6-phosphate dehydrogenase deficiency and hemolytle anemia. In: Nathan D.G ., Orkin S.H ., Ginsburg D. , Look A. T ., (Editors)Nathan and Oski's Hematology of Infancy and Childhood, Sixth ed ., New York, Saunders, 2003; 17:721-38
5. Beutler E. The molecular biology of G6PD variants and other red cell enzyme defects. Ann Rev Med 1992; 43: 47-59.
6. Hassan M K, Taha J Y, Al-Naama L M, Widad N M, and Jasim S N.6.Frequency of hemoglobinopathies and glucose -6- phosphate dehydrogenase deficiency in Basra. Eastern Mediterranean health journal, 2003; 9:49-53.
7. Margaret JA, Adams MJ, Naylor CE. Glucose-6-phsphate dehydrogenase mutationcausingenzymedeficiency,Blood 1996; 87; 2974-2982 .
8. Mehta deficiency. A,Mason Baillieres PJ,Best Vulliamy Pract Res TJ. Clin Glucose-6-phosphate Haematol 2000; 13: 21-38.dehydrogenase.
9. Chen E Y, "Sequence of human glucose-6-phosphate dehydrogenase cloned in plasmids and a yeast artificial chromosome"Genomics1991; 10:792
10. Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Hyperbilirubinemia: Insights on Pathophysiology, Diagnosis, and Gene Variants in Disease Heterogeneity Heng Yang Lee1, Azlin Ithnin2, Raja Zahratul Azma2, Ainoon Othman3, Armindo Salvador4,5,6 and Fook Choe Cheah1*
11. Greco C, Arnolda G, Boo NY, Iskander IF, Okolo AA, Rohsiswatmo R, et al. Neonatal jaundice in low- and middle-income countries: lessons and future directions from the 2015 Don Ostrow Trieste Yellow Retreat. Neonatology. (2016) 110:172–80. doi: 10.1159/000445708
12. Lie-Injo LE, Virik HK, Lim PW, Lie AK, Ganesan J. Red cell metabolism and severe neonatal jaundice in WestMalaysia. Acta Haematol. (1977) 58:152–60. doi: 10.1159/000207822
13. Singh H. Glucose-6-phosphate dehydrogenase deficiency: a preventable cause of mental
retardation. Br Med J (Clin Res Ed). (1986) 292:397–8. doi: 10.1136/bmj.292.6517.397
14. Wong FL, Ithnin A, Othman A, Cheah FC. Glucose-6-phosphate dehydrogenase (G6PD)-deficient infants: enzyme activity and gene variants as risk factors for phototherapy in the first week of life. J Paediatr Child
15. Health. (2017) 53:705–10. doi: 10.1111/jpc.13509
16. Kaplan M, Wong RJ, Stevenson DK. Hemolysis and glucose-6-phosphate dehydrogenase deficiency-related neonatal hyperbilirubinemia. Neonatology. (2018) 114:223–5. doi: 10.1159/000489820
17. Pandolfi PP, Sonati F, Rivi R, Mason P, Grosveld F, Luzzatto L. Targeted disruption of the housekeeping gene encoding glucose 6-phosphate dehydrogenase (G6PD): G6PD is dispensable for pentose synthesis but essential for defense against oxidative stress. EMBO J. (1995) 14:5209–15. doi: 10.1002/j.1460 2075.1995.tb00205.x
18. Low FM, Hampton MB, Winterbourn CC. Peroxiredoxin 2 and peroxide metabolism in the erythrocyte. Antioxid Redox Signal. (2008) 10:1621–30. doi: 10.1089/ars.2008.2081
19. Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. (2009) 30:1–12. doi: 10. 1016/j.mam.2008.08.006
20. Luzzatto L, Arese P. Favism and glucose-6-phosphate dehydrogenase deficiency. N Engl J Med. (2018) 378:60–71. doi: 10.1056/nejmra1708111
21. Cheah FC, Peskin AV, Wong FL, Ithnin A, Othman A, Winterbourn CC. Increased basal oxidation of peroxiredoxin 2 and limited peroxiredoxin recycling in glucose-6-phosphate dehydrogenase-deficient erythrocytes from newborn infants. FASEB J. (2014) 28:3205–10. doi: 10.1096/fj.14-250050
22. Beutler E. The genetics of glucose-6-phosphate dehydrogenase deficiency. Semin Hematol. (1990) 27:137–64.
23. Coelho PMBM, Salvador A, Savageau MA. Relating mutant genotype to phenotype via quantitative behavior of the NADPH redox cycle in human erythrocytes. PLoS One. (2010) 5:e13031. doi: 10.1371/journal.pone.0013031
24. Corrons JL, Alvarez R, Pujades A, Zarza R, Oliva E, Lasheras G, et al. Hereditary non-spherocytic haemolytic anaemia due to red blood cell glutathione synthetase deficiency in four unrelated patients from Spain: clinical and molecular studies. Br J Haematol. (2001) 112:475–82. doi: 10. 1046/j.1365-2141.2001.02526.x
25. Minucci A, Moradkhani K, Hwang MJ, Zuppi C, Giardina B, Capoluongo E. Glucose-6-phosphate dehydrogenase (G6PD) mutations database:review of the “old” and update of the new mutations. Blood Cells Mol Dis. (2012) 48:154–65. doi: 10.1016/j.bcmd.2012.01.001
26. Gómez-Manzo S, Marcial-Quino J, Vanoye-Carlo A, Serrano-Posada H, Ortega-Cuellar D, González-Valdez A, et al. Glucose-6-phosphate dehydrogenase: update and analysis of new mutations around the world. Int J Mol Sci. (2016) 17:2069. doi: 10.3390/ijms17122069
27. Bahr TM, Lozano-Chinga M, Agarwal AM, Meznarich JA, Yost CC, Li P, et al. A novel variant in G6PD (c.1375C>G) identified from a Hispanic neonate with extreme hyperbilirubinemia and low G6PD enzymatic activity. Neonatology. (2020) 117:532–5. doi: 10.1159/000510300
28. Tong Y, Liu B, Zheng H, Bao A, Wu Z, Gu J, et al. A novel G6PD deleterious variant identified in three families with severe glucose-6- phosphate dehydrogenase deficiency. BMC Med Genet. (2020) 21:150. doi:10.1186/s12881-020-01090-2
29. Alina MF, Azma RZ, Norunaluwar J, Azlin I, Darnina AJ, Cheah FC, et al. Genotyping of Malaysian G6PD-deficient neonates by reverse dot blot flowthrough hybridisation. J Hum Genet. 65(3), 263-270. Erratum in J Hum Genet. (2020) 65:635. doi: 10.1038/s10038-019-0700-7
30. Malik S, Zaied R, Syed N, Jithesh P, Al-Shafai M. Seven novel glucose- 6-phosphate dehydrogenase (G6PD) deficiency variants identified in the Qatari population. Hum Genomics. (2021) 15:61. doi: 10.1186/s40246-021-0 0358-9
31. Xu W, Westwood B, Bartsocas CS, Malcorra-Azpiazu JJ, Indrák K, Beutler E. Glucose-6 phosphate dehydrogenase mutations and haplotypes in various ethnic groups. Blood (1995) 85:257–63. doi: 10.1182/blood.V85. 1.257.bloodjournal851257
32. Chen TL, Yang HC, Hung CY, Ou MH, Pan YY, Cheng ML, et al. Impaired embryonic development in glucose-6-phosphate dehydrogenasedeficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism. Cell Death Dis. (2017) 8:e2545. doi: 10. 1038/cddis.2016.463
33. Yoshida A, Beutler E, Motulsky AG. Human glucose-6-phosphate dehydrogenase variants. Bull World Health Organ. (1971) 45:243–53.
34. He Y, Zhang Y, Chen X, Wang Q, Ling L, Xu Y. Glucose-6-phosphate dehydrogenase deficiency in the Han Chinese population: molecular characterization and genotype-phenotype association throughout an activity distribution. Sci Rep. (2017) 10:17106. doi: 10.1038/s41598-020-74200-y
35. Boonyuen U, Chamchoy K, Swangsri T, Saralamba N, Day NP, Imwong M. Detailed functional analysis of two clinical glucose-6- phosphate dehydrogenase (G6PD) variants, G6PDViangchan and G6PDViangchan+Mahidol: decreased stability and catalytic efficiency contribute to the clinical phenotype. Mol Genet Metab. (2016) 118:84–91. doi: 10.1016/j.ymgme.2016.03.008
36. Pietrapertosa A, Palma A, Campanale D, Delios G, Vitucci A, Tannoia N. Genotype and phenotype correlation in glucose-6-phosphate dehydrogenase deficiency. Haematologica. (2001) 86:30–5.
37. Scopes DA, Bautista JM, Naylor CE, Adams MJ, Mason PJ. Amino acid substitutions at the dimer interface of human glucose-6-phosphate dehydrogenase that increase thermostability and reduce the stabilising effect of NADP. Eur J Biochem. (1998) 251:382–8. doi: 10.1046/j.1432-1327.1998. 2510382.x
38. Mason PJ, Bautista JM, Gilsanz F. G6PD deficiency: the genotype-phenotype association. Blood Rev. (2007) 21:267–83. doi: 10.1016/j.blre.2007.05.002
39. Gómez-Manzo S, Terrón-Hernández J, De la Mora-De la Mora I, González-Valdez A, Marcial-Quino J, García-Torres I, et al. The stability of G6PD is affected by mutations with different clinical phenotypes. Int J Mol Sci. (2014) 15:21179–201. doi: 10.3390/ijms151121179
40. Ainoon O, Alawiyah A, Yu YH, Cheong SK, Hamidah NH, Boo NY, et al. Semiquantitative screening test for G6PD deficiency detects severe deficiency but misses a substantial proportion of partiallydeficient females. Southeast Asian J Trop Med Public Health. (2003)34:405–14.
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Jun 20, 2023
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Myasar Hafedh Ibrahim, Ibrahim Mahmood Saeed, & Sundus Mohammed Hussein. (2023). G6pd Deficiency And Hyperbilirubinemia In Newborn Baby(Prospective Study ). Journal of Population Therapeutics and Clinical Pharmacology, 30(15), 189–198. https://doi.org/10.47750/jptcp.2023.30.15.021
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